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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(4): 845-852, 2024 Jul 20.
Article in Chinese | MEDLINE | ID: mdl-39170016

ABSTRACT

Objective: To design and prepare a high efficiency bilirubin adsorbent with good mechanical properties and biocompatibility. Methods: In this study, quaternary ammonium pyridine was designed and synthesized, and then modified polyether sulfone microspheres, or PES/p(4-VP-co-N-VP)@6 microspheres, were prepared by phase conversion and electrostatic spraying. The morphology of the polymer components and the microspheres were studied by means of nuclear magnetic resonance (NMR) spectroscopy and scanning electron microscopy. The basic properties of the microspheres and their bilirubin adsorption efficiency were tested, and the adsorption mechanism was further explored. Blood cell counts and the clotting time of the microspheres were also measured. Results: The diameter of the modified polyether sulfone microspheres prepared in the study was approximately 700-800 µm. Compared with the original PES microspheres, the surface and internal structure of PES/p(4-VP-co-N-VP)@6 microspheres did not change significantly, and they also had a loose porous structure, with some micropores scattered around in addition to irregular large pores. Compared with the control group, the bilirubin removal effect of the modified microspheres was (94.91±0.73)% after static adsorption in bilirubin PBS buffer solution for 180 min, with the difference being statistically significant (P<0.0001). According to the findings for the clotting time, the activated partial thromboplastin time (APTT) of the blank plasma group, the control PES group, and the modified PES microsphere group were (27.57±1.25) s, (28.47±0.45) s, and (30.4±0.872) s, respectively, and the difference between the experimental group and the other two groups was statistically significant (P<0.01, P<0.05). There was no significant change in red blood cell and white blood cell counts. Conclusion: The microspheres prepared in the study have high efficiency in bilirubin adsorption, excellent mechanical properties and thermal stability, and good blood biocompatibility, and are expected to be used in the clinical treatment of patients with liver failure.


Subject(s)
Bilirubin , Microspheres , Polymers , Sulfones , Sulfones/chemistry , Polymers/chemistry , Adsorption , Bilirubin/blood , Humans
2.
J Environ Manage ; 367: 122069, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39098071

ABSTRACT

Studying the adsorption behavior of cationic surfactants can help to develop more effective strategies to limit their dispersion in the environment. However, there have few studies on the adsorption of cationic surfactants from the perspective of critical micelle concentration (CMC). In this study, with cetyltrimethylammonium bromide (CTAB) and octadecyl trimethylammonium bromide (OTAB) serving as the model cationic surfactants, the effect of CMC on the adsorption behavior of cationic surfactant onto the surface of sodium alginate/silica (SA/SiO2) microspheres was systematically revealed. The adsorption mechanism relative to CMC was investigated under different conditions, including surfactant concentration, pH, temperature, and adsorption time. The results suggest that at identical concentrations, the smaller the CMC value of the cationic surfactants, the greater the adsorption amount (qt). qt for CTAB and OTAB were 583.2 and 678.0 mg/g respectively, with the concentration higher than their CMC value. When the concentration was lower than the CMC value of the cationic surfactants, qt for CTAB and OTAB were 123.2 and 138.7 mg/g, respectively. The CMC value of CTAB was lower than that of OTAB under identical conditions, suggesting that the adsorption of cationic surfactants is related to their CMC. These results are beneficial for the removal of cationic surfactants by adsorption methods.


Subject(s)
Cations , Micelles , Microspheres , Silicon Dioxide , Surface-Active Agents , Surface-Active Agents/chemistry , Adsorption , Silicon Dioxide/chemistry , Cations/chemistry , Cetrimonium/chemistry , Cetrimonium Compounds/chemistry , Alginates/chemistry , Hydrogen-Ion Concentration
3.
Langmuir ; 40(33): 17463-17475, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39105736

ABSTRACT

Despite national and international regulations, plastic microbeads are still widely used in personal care and consumer products (PCCPs). These exfoliants and rheological modifiers cause significant microplastic pollution in natural aquatic environments. Microbeads from nonderivatized biomass like cellulose and lignin can offer a sustainable alternative to these nondegradable microplastics, but processing this biomass into microbeads is challenging due to limited viable solvents and high biomass solution viscosities. To produce biomass microbeads of the appropriate size range for PCCPs (ca. 200-800 µm diameter) with shapes and mechanical properties comparable to those of commercial plastic microbeads, we used a surfactant-free emulsion/precipitation method, mixing biomass solutions in 1-ethyl-3-methylimidazolium acetate (EMImAc) with various oils and precipitating with ethanol. While yield of microbeads within the target size range highly depends on purification conditions, optimized protocols led to >90% yield of cellulose microbeads. Kraft lignin was then successfully incorporated into beads at up to 20 wt %; however, higher lignin contents result in emulsion destabilization unless surfactant is added. Finally, the microbead shape and surface morphology can be tuned using oils of varying viscosities and interfacial tensions. Dripping measurements and pendant drop tensiometry confirmed that the higher affinity of cellulose for certain oil/IL interfaces largely controlled the observed surface morphology. This work thus outlines how biomass composition, oil viscosity, and interfacial properties can be altered to produce more sustainable microbeads for use in PCCPs, which have desirable mechanical properties and can be produced over a wide range of shapes and surface morphologies.


Subject(s)
Biomass , Cellulose , Emulsions , Microspheres , Emulsions/chemistry , Cellulose/chemistry , Lignin/chemistry , Imidazoles/chemistry , Particle Size , Surface-Active Agents/chemistry
4.
Anal Chem ; 96(33): 13636-13643, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39110483

ABSTRACT

In recent years, optical tweezers have become an effective bioassay tool due to their unique advantages, especially in combination with suspension beads, which can be applied to develop a high-performance analysis platform capable of high-quality imaging and stable signal output. However, the optical tweezer-assisted bead analysis is still at the early stage, and further development of different favorable methods is in need. Herein, we have first developed the optical tweezer-assisted immuno-rolling circle amplification (immuno-RCA) on beads for protein detection. Prostate-specific antigen was selected as the model analyte, and the immunosandwich structure on beads was built by the high affinity of "antibody-antigen". The "protein-nucleic acid" signals were effectively converted through the covalent coupling procedure of antibodies and oligonucleotides, further initiating the RCA reaction to achieve signal amplification. The individual beads with the strong irregular Brownian motion in a fluid environment were eventually trapped by the optical tweezers to acquire the accurate and high-quality signal. Compared with the conventional immunoassay on beads, the sensitivity of the developed strategy was increased by 587 times with a limit of detection of 4.29 pg/mL (0.13 pM), as well as excellent specificity, stability, and reproducibility. This study developed the new optical tweezer-assisted beads imaging strategy for protein targets, which has great potential for being applied to clinical serology research and expands the application of optical tweezers in the bioassays.


Subject(s)
Optical Tweezers , Prostate-Specific Antigen , Prostate-Specific Antigen/analysis , Humans , Nucleic Acid Amplification Techniques , Immunoassay/methods , Limit of Detection , Microspheres , Biosensing Techniques/methods
5.
Technol Cancer Res Treat ; 23: 15330338241274289, 2024.
Article in English | MEDLINE | ID: mdl-39149935

ABSTRACT

Introduction: In recent years, the development of drug-eluting embolization beads that can be imaged has become a hot research topic in regard to meeting clinical needs. In our previous study, we successfully developed nano-assembled microspheres (NAMs) for multimodal imaging purposes. NAMs can not only be visualized under CT/MR/Raman imaging but can also load clinically required doses of doxorubicin. It is important to systematically compare the pharmacokinetics of NAMs with those of commercially available DC Beads and CalliSpheres to evaluate the clinical application potential of NAMs. Methods: In our study, we compared NAMs with two types of drug-eluting beads (DEBs) in terms of irinotecan, drug-loading capacity, release profiles, microsphere diameter variation, and morphological characteristics. Results: Our results indicate that NAMs had an irinotecan loading capacity similar to those of DC Beads and CalliSpheres but exhibited better sustained release in vitro. Conclusion: NAMs have great potential for application in transcatheter arterial chemoembolization for the treatment of colorectal cancer liver metastases.


Subject(s)
Irinotecan , Microspheres , Multimodal Imaging , Irinotecan/administration & dosage , Irinotecan/pharmacology , Humans , Multimodal Imaging/methods , Drug Carriers/chemistry , Drug Liberation , Chemoembolization, Therapeutic/methods , Drug Delivery Systems , Liver Neoplasms/secondary , Liver Neoplasms/drug therapy , Liver Neoplasms/diagnostic imaging , Camptothecin/analogs & derivatives , Camptothecin/administration & dosage , Camptothecin/pharmacology
6.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 40: e20240019, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39103243

ABSTRACT

OBJECTIVE: This work is aimed to Formulate, Optimize and Evaluate Gastro-Retentive Microspheres of Antidiabetic Agent by Full Factorial Design. METHODS: Microspheres were prepared using Emulsification-cross linking technique. To this HPMC-K4M and Carbopol was dissolved in 250 ml of water and allowed to swell for 24 hr at room temperature. And separately chitosan was dissolved in 3% (v/v) glacial acetic acid and this also kept for 24 h to swell or dissolve properly. After 24hr this swelled mixture was mixed under magnetic stirrer (Remi, India) at specific stirring rate for 1hr in order to find homogeneous mass of both the gum. Then slurry of chitosan also was homogenized for half an hour. The drug, Glipizide (1g) was then added to the chitosan solution and mixed homogenesously. RESULTS: The aim of the study was to formulate and evaluate microspheres, for Gastro-Retentive Microspheres of the chosen drug. The EE of microspheres was found to be 91.52%, maximum . Buoyancy property observed was 93.82% for Optimized formulation F-9, Drug release 57.34% till 8 h. The work also aims to study various parameters affecting the behaviour of microspheres in oral dosage form. CONCLUSION: Drugs with short half-life that are absorbed from the gastrointestinal tract (GIT) are eliminated rapidly from the blood flow. To avoid this, the oral SR Gastro-retentive was developed as this formulation released the drug slowly into the GIT and maintained a stable drug concentration in the serum for a longer duration of time.


Subject(s)
Chitosan , Hypoglycemic Agents , Microspheres , Hypoglycemic Agents/administration & dosage , Chitosan/chemistry , Drug Stability , Delayed-Action Preparations , Animals , Rats , Glipizide/administration & dosage , Glipizide/pharmacokinetics
7.
Drug Dev Res ; 85(5): e22247, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39138857

ABSTRACT

Inflammatory diseases including rheumatoid arthritis are major health problems. Although different techniques and drugs are clinically available for the diagnosis and therapy of the disease, novel approaches regarding radiolabeled drug delivery systems are researched. Hence, in the present study, it was aimed to design, prepare, and characterize 99mTc-radiolabeled and tofacitinib citrate-encapsulated microsphere loaded poloxamer in situ gel formulations for the intra-articular treatment. Among nine different microsphere formulations, MS/TOFA-9 was chosen as the most proper one due to particle size, high encapsulation efficiency, and in vitro drug release behavior. Poloxamer 338 at a concentration of 15% was used to prepare in situ gel formulations. For intra-articular administration, microspheres were dispersed in an in situ gel containing 15% Poloxamer 338 and characterized in terms of gelation temperature, viscosity, rheological, mechanical, and spreadability properties. After the determination of the safe dose for MS/TOFA-9 and PLX-MS/TOFA-9 as 40 µL/mL in the cell culture study performed on healthy cells, the high anti-inflammatory effects were due to significant cellular inhibition of fibroblasts. In the radiolabeling studies with 99mTc, the optimum radiolabeling condition was determined as 200 ppm SnCl2 and 0.5 mg ascorbic acid, and both 99mTc-MS/TOFA-9 and 99mTc-PLX-MS/TOFA-9 exhibited high cellular binding capacity. In conclusion, although further in vivo experiments are required, PLX-MS/TOFA-9 was found to be a promising agent for intra-articular injection in rheumatoid arthritis.


Subject(s)
Arthritis, Rheumatoid , Chitosan , Gels , Microspheres , Piperidines , Pyrimidines , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/diagnostic imaging , Pyrimidines/chemistry , Pyrimidines/administration & dosage , Pyrimidines/pharmacokinetics , Piperidines/chemistry , Piperidines/administration & dosage , Piperidines/pharmacokinetics , Chitosan/chemistry , Humans , Technetium/chemistry , Injections, Intra-Articular , Pyrroles/chemistry , Pyrroles/administration & dosage , Animals , Poloxamer/chemistry , Particle Size , Drug Liberation
8.
Bull Environ Contam Toxicol ; 113(2): 24, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39126490

ABSTRACT

Microplastics merit attention as they can be ingested by lower trophic organisms, transferred to the food web, and pose potential risks to higher trophic levels. This study investigated the accumulation and effects of polyethylene microbeads (PEMBs, 63-75 µm) on adult water flea Moina macrocopa (600-800 µm), an order-magnitude difference in size, as a result of acute exposure. The organisms were exposed to PEMBs in four treatments of 0 (the Control), 5, 50, and 500 mg PEMB/L for examining PEMB accumulation, survival and reproduction of the organisms after the 24- and 48-h exposures. In general, M. macrocopa ingested PEMBs within 24-h exposure and reached the cumulative PEMB accumulation value of 0.17 ± 0.21 beads/adult after 48-h exposure in the 500 mg PEMB/L treatment. Exposure to PEMBs resulted in a statistically significant decrease of the cumulative survival rates, from 93 ± 12% in the Control to 37 ± 21% in the 500 mg/L treatment. Nevertheless, exposure to PEMBs did not significantly reduce the cumulative reproduction (p > 0.05), although a decrease was observed. This study suggests that the relatively large-size PEMBs could be ingested by the relatively small-size M. macrocopa and pose potential risks to these organisms.


Subject(s)
Polyethylene , Water Pollutants, Chemical , Animals , Polyethylene/toxicity , Water Pollutants, Chemical/toxicity , Microplastics/toxicity , Microspheres , Cladocera/drug effects , Cladocera/physiology , Reproduction/drug effects
9.
Molecules ; 29(15)2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39124874

ABSTRACT

Developing reusable and easy-to-operate biocatalysts is of significant interest in biodiesel production. Here, magnetic whole-cell catalysts constructed through immobilizing recombinant Escherichia coli cells (containing MAS1 lipase) into Fe3O4-chitosan magnetic microspheres (termed MWCC@MAS1) were used for fatty acid methyl ester (FAME) production from waste cooking oil (WCO). During the preparation process of immobilized cells, the effects of chitosan concentration and cell concentration on their activity and activity recovery were investigated. Optimal immobilization was achieved with 3% (w/v) chitosan solution and 10 mg wet cell/mL cell suspension. Magnetic immobilization endowed the whole-cell catalysts with superparamagnetism and improved their methanol tolerance, enhancing the recyclability of the biocatalysts. Additionally, we studied the effects of catalyst loading, water content, methanol content, and reaction temperature on FAME yield, optimizing these parameters using response surface methodology and Box-Behnken design. An experimental FAME yield of 89.19% was gained under the optimized conditions (3.9 wt% catalyst loading, 22.3% (v/w) water content, 23.0% (v/w) methanol content, and 32 °C) for 48 h. MWCC@MAS1 demonstrated superior recyclability compared to its whole-cell form, maintaining about 86% of its initial productivity after 10 cycles, whereas the whole-cell form lost nearly half after just five cycles. These results suggest that MWCC@MAS1 has great potential for the industrial production of biodiesel.


Subject(s)
Biofuels , Chitosan , Escherichia coli , Microspheres , Escherichia coli/genetics , Escherichia coli/metabolism , Chitosan/chemistry , Cells, Immobilized/metabolism , Plant Oils/chemistry , Lipase/metabolism , Lipase/genetics , Methanol/chemistry , Cooking
10.
Korean J Radiol ; 25(8): 715-725, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39109500

ABSTRACT

OBJECTIVE: To evaluate the outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) according to the size of the beads for the treatment of small hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 212 patients with a single HCC ≤5 cm from five tertiary institutions. One hundred and nine patients were treated with 70-150-µm doxorubicin DEBs (group A), and 103 patients received 100-300-µm doxorubicin DEBs (group B). The initial tumor response (assessed between 3 weeks and 2 months after DEB-TACE), time to local tumor progression (TTLTP), restricted mean duration of complete response (RMDCR), rate of complications, incidence of post-embolization syndrome, and length of hospital stay were compared between the two groups. Logistic regression was used to analyze prognostic factors for initial tumor response. RESULTS: The initial objective response rates were 91.7% (100/109) and 84.5% (87/103) for groups A and B, respectively (P = 0.101). In the subgroup analysis of tumors ≤3 cm, the initial objective response rates were 94.6% (53/56) and 78.0% (39/50) for groups A and B, respectively (P = 0.012). There was no significant difference in the TTLTP (median, 23.7 months for group A vs. 19.0 months for group B; P = 0.278 [log-rank], 0.190 [multivariable Cox regression]) or RMDCR at 24 months (11.4 months vs. 8.5 months, respectively; P = 0.088). In the subgroup analysis of tumors >3-cm, the RMDCR at 24 months was significantly longer in group A than in group B (11.8 months vs. 5.7 months, P = 0.024). The incidence of mild bile duct dilatation after DEB-TACE was significantly higher in group B than in group A (5.5% [6/109] vs. 18.4% [19/103], P = 0.003). CONCLUSION: DEB-TACE using 70-150-µm microspheres demonstrated a higher initial objective response rate in ≤3-cm HCCs and a longer RMDCR at 24 months in 3.1-5-cm HCCs compared to larger DEBs (100-300-µm).


Subject(s)
Antibiotics, Antineoplastic , Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Doxorubicin , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/diagnostic imaging , Liver Neoplasms/therapy , Liver Neoplasms/diagnostic imaging , Chemoembolization, Therapeutic/methods , Male , Female , Middle Aged , Retrospective Studies , Doxorubicin/administration & dosage , Treatment Outcome , Republic of Korea , Aged , Antibiotics, Antineoplastic/administration & dosage , Microspheres , Adult
11.
Methods Mol Biol ; 2835: 325-337, 2024.
Article in English | MEDLINE | ID: mdl-39105928

ABSTRACT

Gelatin, a protein derivative from collagen, is a versatile material with promising applications in tissue engineering. Among the various forms of gelatin scaffolds, nanofibrous gelatin microspheres (NFGMs) are attracting research efforts due to their fibrous nature and injectability. However, current methods for synthesizing nanofibrous gelatin microspheres (NFGMs) have limitations, such as wide size distributions and the use of toxic solvents. To address these challenges, the article introduces a novel approach. First, it describes the creation of a microfluidic device using readily available supplies. Subsequently, it outlines a unique process for producing monodispersed NFGMs through a combination of the microfluidic device and thermally induced phase separation (TIPS). This innovative method eliminates the need for sieving and the use of toxic solvents, making it a more ecofriendly and efficient alternative.


Subject(s)
Gelatin , Microspheres , Nanofibers , Gelatin/chemistry , Nanofibers/chemistry , Tissue Engineering/methods , Microfluidics/methods , Microfluidics/instrumentation , Tissue Scaffolds/chemistry , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods
12.
Methods Mol Biol ; 2829: 277-286, 2024.
Article in English | MEDLINE | ID: mdl-38951344

ABSTRACT

Quantitative immunoassays, such as the traditional enzyme-linked immunosorbent assay (ELISA), are used to determine concentrations of an antigen in a matrix of unknown antigen concentration. Magnetic immunoassays, such as the Luminex xMAP technology, allow for the simultaneous detection of multiple analytes and offer heightened sensitivity, specificity, low sample volume requirements, and high-throughput capabilities. Here, we describe a quantitative immunoassay using the Luminex MAGPIX® System to determine the antigen concentration from liquid samples with unknown concentrations. In detail, we describe a newly developed assay for determining production yields of Drosophila S2-produced Marburg virus (MARV) glycoprotein in insect-cell-culture-derived supernatant. The potential applications of this assay could extend to the quantification of viral antigens in fluids derived from both in vitro and in vivo models infected with live MARV, thereby providing additional applications for virological research.


Subject(s)
Antigens, Viral , Microspheres , Animals , Immunoassay/methods , Antigens, Viral/immunology , Antigens, Viral/analysis , Marburgvirus/immunology , Marburgvirus/isolation & purification , Drosophila , Cell Culture Techniques/methods , Cell Line , Enzyme-Linked Immunosorbent Assay/methods
13.
AAPS PharmSciTech ; 25(6): 162, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38997615

ABSTRACT

In 1987, Won invented the solid-phase porous microsphere (MS), which stores bioactive compounds in many interconnected voids. Spherical particles (5-300 µm), MS, may form clusters of smaller spheres, resulting in many benefits. The current investigation focussed on gel-encased formulation, which can be suitable for dermal usage. First, quasi-emulsion (w/o/w) solvent evaporation was used to prepare 5-fluorouracil (5 FU) MS particles. The final product was characterized (SEM shows porous structure, FTIR and DSC showed drug compatibility with excipients, and gel formulation is shear-thinning) and further scaled up using the 8-fold method. Furthermore, CCD (Central Composite Design) was implemented to obtain the optimized results. After optimizing the conditions, including the polymer (600 mg, ethyl cellulose (EC), eudragit RS 100 (ERS)), stirring speed (1197 rpm), and surfactant concentration (2% w/v), we achieved the following results: optimal yield (63%), mean particle size (152 µm), drug entrapment efficiency (76%), and cumulative drug release (74.24% within 8 h). These findings are promising for industrial applications and align with the objectives outlined in UN Sustainable Development Goals 3, 9, and 17, as well as the goals of the G20 initiative.


Subject(s)
Drug Delivery Systems , Drug Liberation , Fluorouracil , Microspheres , Particle Size , Fluorouracil/administration & dosage , Fluorouracil/chemistry , Drug Delivery Systems/methods , Porosity , Emulsions/chemistry , Cellulose/chemistry , Cellulose/analogs & derivatives , Chemistry, Pharmaceutical/methods , Polymers/chemistry , Excipients/chemistry , Solvents/chemistry , Surface-Active Agents/chemistry , Acrylic Resins/chemistry , Drug Carriers/chemistry , Gels/chemistry
14.
ACS Nano ; 18(28): 18425-18443, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38975713

ABSTRACT

Tumor in situ vaccination (ISV) strategies have emerged in clinical trials as promising approaches, involving the release of tumor antigens through local radiotherapy and intratumorally adjuvant injections. However, the current fabrication strategy for achieving a sustainable immune response to ISV remains a pressing challenge. In this study, we present an empowered sustainable ISV method for antitumor therapy using 177Lu-labeled manganese-doped mesoporous hydroxyapatite (177Lu/Mn-HAP) microspheres. The ISV enables the sustained utilization of tumor antigens, leading to the activation of dendritic cells and polarization of macrophages toward the M1 subtype. Consequently, it facilitates the generation of potent CD8+ T-cell responses, enhancing the antitumor effects of internal radiation in both primary and distant tumors. Importantly, this approach achieves complete remission in all tumor-bearing mice and stimulates immune memory to prevent tumor recurrence. Our study highlights a universal and safe ISV strategy capable of inducing potent tumor-specific and sustainable immune response.


Subject(s)
Cancer Vaccines , Durapatite , Microspheres , Durapatite/chemistry , Animals , Mice , Cancer Vaccines/immunology , Cancer Vaccines/chemistry , CD8-Positive T-Lymphocytes/immunology , Vaccination , Female , Mice, Inbred C57BL , Radioisotopes/chemistry , Cell Line, Tumor
15.
Nano Lett ; 24(28): 8752-8762, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38953881

ABSTRACT

Acute methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a common and serious lung infection with high morbidity and mortality rates. Due to the increasing antibiotic resistance, toxicity, and pathogenicity of MRSA, there is an urgent need to explore effective antibacterial strategies. In this study, we developed a dry powder inhalable formulation which is composed of porous microspheres prepared from poly(lactic-co-glycolic acid) (PLGA), internally loaded with indocyanine green (ICG)-modified, heat-resistant phages that we screened for their high efficacy against MRSA. This formulation can deliver therapeutic doses of ICG-modified active phages to the deep lung tissue infection sites, avoiding rapid clearance by alveolar macrophages. Combined with the synergistic treatment of phage therapy and photothermal therapy, the formulation demonstrates potent bactericidal effects in acute MRSA pneumonia. With its long-term stability at room temperature and inhalable characteristics, this formulation has the potential to be a promising drug for the clinical treatment of MRSA pneumonia.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Polylactic Acid-Polyglycolic Acid Copolymer , Methicillin-Resistant Staphylococcus aureus/drug effects , Animals , Mice , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Microspheres , Photothermal Therapy , Pneumonia, Staphylococcal/therapy , Phage Therapy/methods , Indocyanine Green/chemistry , Indocyanine Green/pharmacology , Indocyanine Green/therapeutic use , Indocyanine Green/administration & dosage , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Administration, Inhalation , Humans , Bacteriophages/chemistry
16.
Int J Biol Macromol ; 276(Pt 1): 133821, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38996892

ABSTRACT

Osteoporotic bone defects are serious medical problems due to their sparse bone structure, difficulty in restoration and reconstruction, and high recurrence rates, which also result in heavy economic and social burdens. Herein, we developed a hierarchical hydrogel composed of alendronate sodium (AS)/Mg2+-loaded inverse opal methylpropenylated gelatin (GelMA) hydrogel microspheres (IOHM-AS-Mgs) within methylpropenylated poly(hyaluronic acid) (HAMA) for osteoporotic bone defect treatment. The IOHM-AS-Mgs displayed good cytocompatibility and cell adhesion and strongly stimulated osteogenesis at the transcriptomic and protein levels. When this treatment was applied to the osteoporotic bone defect area, HAMA was used to fix the microspheres. The results of the microcomputed tomography (micro-CT) and histological analyses indicated that the hierarchical hydrogel had the best therapeutic effect. Therefore, this hydrogel is a new candidate for osteoporotic bone defect treatment.


Subject(s)
Alendronate , Gelatin , Hyaluronic Acid , Hydrogels , Osteogenesis , Osteoporosis , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Gelatin/chemistry , Animals , Hydrogels/chemistry , Osteoporosis/drug therapy , Alendronate/pharmacology , Alendronate/chemistry , Osteogenesis/drug effects , Microspheres , X-Ray Microtomography , Bone Regeneration/drug effects , Mice , Humans
17.
Int J Biol Macromol ; 276(Pt 1): 133835, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39002901

ABSTRACT

Efficient treatment of toxic organic pollutants in water/wastewater by using innovative, cost efficient, and simple technologies has recently become an important issue worldwide. Remediation of these pollutants with chemical reduction in the presence of a nano-sized catalyst and a reducing agent is one of the most useful methodologies. In the present study, we have designed a promising heterogeneous catalyst system (Pd@CS-NiO) by easy and efficient stabilization of palladium nanoparticles on the surface of microspheres composed of chitosan (CS)-NiO particles (CS-NiO) for the reduction of organic pollutants. The nano-structure of the developed Pd@CS-NiO was successfully validated using FE-SEM, XRD, EDS, TEM, and FTIR/ATR and its particles size was determined as 10 nm. The catalytic power of Pd@CS-NiO was then assessed in the reduction of 4-nitro-o-phenylenediamine (4-NPDA), 4-nitrophenol (4-NP), 4-nitroaniline (4-NA), 2-nitroaniline (2-NA), and some organic dyes, namely methylene blue (MB), methyl orange (MO), and rhodamine B (RhB) in aqueous medium at room temperature. The reductions were thoroughly studied spectro-photometrically. The tests displayed that the synthesized Pd@CS-NiO was a highly active and useful catalyst that reduced these pollutants in 0-145 s. Moreover, the rate constants for 2-NA, 4-NP, 4-NA, 4-NPDA, MO, and RhB were found to be 0.017 s-1, 0.011 s-1, 0.006 s-1, 0.013 s-1, 0.023 s-1, and 0.03 s-1, respectively. Moreover, the recycling test indicated that Pd@CS-NiO may be recovered easily thanks to its micro size nature and could be used up to seven steps, confirming its practical application potential.


Subject(s)
Chitosan , Metal Nanoparticles , Nickel , Palladium , Chitosan/chemistry , Palladium/chemistry , Catalysis , Metal Nanoparticles/chemistry , Nickel/chemistry , Microspheres , Water Pollutants, Chemical/chemistry , Environmental Pollutants/chemistry , Particle Size , Water Purification/methods
18.
Int J Mol Sci ; 25(14)2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39063114

ABSTRACT

The aim of this study was to examine the use of zwitterionic microparticles as new and efficient macromolecular supports for the sorption of an antibiotic (doxycycline hydrochloride, DCH) from aqueous solution. The effect of relevant process parameters of sorption, like dosage of microparticles, pH value, contact time, the initial concentration of drug and temperature, was evaluated to obtain the optimal experimental conditions. The sorption kinetics were investigated using Lagergren, Ho, Elovich and Weber-Morris models, respectively. The sorption efficiency was characterized by applying the Langmuir, Freundlich and Dubinin-Radushkevich isotherm models. The calculated thermodynamic parameters (ΔH, ΔS and ΔG) show that the sorption of doxycycline hydrochloride onto zwitterionic microparticles is endothermic, spontaneous and favorable at higher temperatures. The maximum identified sorption capacity value is 157.860 mg/g at 308 K. The Higuchi, Korsmeyer-Peppas, Baker-Lonsdale and Kopcha models are used to describe the release studies. In vitro release studies show that the release mechanism of doxycycline hydrochloride from zwitterionic microparticles is predominantly anomalous or non-Fickian diffusion. This study could provide the opportunity to expand the use of these new zwitterionic structures in medicine and water purification.


Subject(s)
Betaine , Doxycycline , Doxycycline/chemistry , Betaine/chemistry , Kinetics , Adsorption , Thermodynamics , Hydrogen-Ion Concentration , Anti-Bacterial Agents/chemistry , Drug Liberation , Temperature , Microspheres
19.
ACS Appl Mater Interfaces ; 16(31): 40555-40569, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39042857

ABSTRACT

Regenerating periodontal defects in osteoporosis patients presents a significant clinical challenge. Unlike the relatively straightforward regeneration of homogeneous bone tissue, periodontal regeneration requires the intricate reconstruction of the cementum-periodontal ligament-alveolar bone interface. Strontium (Sr)-doped biomaterials have been extensively utilized in bone tissue engineering due to their remarkable pro-osteogenic attributes. However, their application in periodontal tissue regeneration has been scarcely explored. In this study, we synthesized an innovative injectable Sr-BGN/GNM scaffold by integrating Sr-doped bioactive glass nanospheres (Sr-BGNs) into the nanofiber architecture of gelatin nanofiber microspheres (GNMs). This design, mimicking the natural bone extracellular matrix (ECM), enhanced the scaffold's mechanical properties and effectively controlled the sustained release of Sr ions (Sr2+), thereby promoting the proliferation, osteogenic differentiation, and ECM secretion of PDLSCs and BMSCs, as well as enhancing vascularization in endothelial cells. In vivo experiments further indicated that the Sr-BGNs/GNMs significantly promoted osteogenesis and angiogenesis. Moreover, the scaffold's tunable degradation kinetics optimized the prolonged release and pro-regenerative effects of Sr2+ in vivo, matching the pace of periodontal regeneration and thereby facilitating the regeneration of functional periodontal tissues under osteoporotic conditions. Therefore, Sr-BGNs/GNMs emerge as a promising candidate for advancing periodontal regeneration strategies.


Subject(s)
Extracellular Matrix , Microspheres , Nanofibers , Osteoporosis , Strontium , Strontium/chemistry , Strontium/pharmacology , Nanofibers/chemistry , Osteoporosis/drug therapy , Humans , Extracellular Matrix/chemistry , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Animals , Osteogenesis/drug effects , Tissue Scaffolds/chemistry , Cell Differentiation/drug effects , Tissue Engineering , Cell Proliferation/drug effects , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/cytology , Regeneration/drug effects
20.
Int J Biol Macromol ; 275(Pt 1): 133557, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38955293

ABSTRACT

Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.


Subject(s)
Alginates , Anti-Bacterial Agents , Bone Morphogenetic Protein 2 , Bone Regeneration , Gelatin , Microspheres , Gelatin/chemistry , Gelatin/pharmacology , Alginates/chemistry , Alginates/pharmacology , Bone Regeneration/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Animals , Bone Morphogenetic Protein 2/pharmacology , Bone Morphogenetic Protein 2/chemistry , Vascular Endothelial Growth Factor A/pharmacology , Vascular Endothelial Growth Factor A/chemistry , Vascular Endothelial Growth Factor A/metabolism , Methacrylates/chemistry , Methacrylates/pharmacology , Mice , Hydrogels/chemistry , Hydrogels/pharmacology , Humans , Drug Liberation
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